Immune Regulatory Neural Stem/Precursor Cells Protect from Central Nervous System Autoimmunity by Restraining Dendritic Cell Function

The systemic injection of neural stem/precursor cells (NPCs) provides remarkable amelioration of the clinico-pathological features of experimental autoimmune encephalomyelitis (EAE). This is dependent on the capacity of transplanted NPCs to engage concurrent mechanisms of action within specific microenvironments in vivo. Among a wide range of therapeutic actions alternative to cell replacement, neuroprotective and immune modulatory capacities of transplanted NPCs have been described. However, lacking is a detailed understanding of the mechanisms by which NPCs exert their therapeutic plasticity. This study was designed to identify the first candidate that exemplifies and sustains the immune modulatory capacity of transplanted NPCs.To achieve the exclusive targeting of the peripheral immune system, SJL mice with PLP-induced EAE were injected subcutaneously with NPCs and the treatment commenced prior to disease onset. NPC-injected EAE mice showed significant clinical improvement, as compared to controls. Exogenous NPCs lacking the expression of major neural antigens were reliably (and for long-term) found at the level of draining lymph nodes, while establishing sophisticated anatomical interactions with lymph node cells. Importantly, injected NPCs were never found in organs other than lymph nodes, including the brain and the spinal cord. Draining lymph nodes from transplanted mice showed focal up-regulation of major developmental stem cell regulators, such as BMP-4, Noggin and Sonic hedgehog. In lymph nodes, injected NPCs hampered the activation of myeloid dendritic cells (DCs) and steadily restrained the expansion of antigen-specific encephalitogenic T cells. Both ex vivo and in vitro experiments identified a novel highly NPC-specific–BMP-4-dependent–mechanism hindering the DC maturation.The study described herein, identifies the first member of the TGF β/BMP family of stem cell regulators as a novel tolerogenic factor released by NPCs. Full exploitation of this pathway as an efficient tool for vaccination therapy in autoimmune inflammatory conditions is underway

Reinterpretation of LHC Results for New Physics: Status and recommendations after Run 2

We report on the status of efforts to improve the reinterpretation of searches and measurements at the LHC in terms of models for new physics, in the context of the LHC Reinterpretation Forum. We detail current experimental offerings in direct searches for new particles, measurements, technical implementations and Open Data, and provide a set of recommendations for further improving the presentation of LHC results in order to better enable reinterpretation in the future. We also provide a brief description of existing software reinterpretation frameworks and recent global analyses of new physics that make use of the current data

The relation between karst spring discharge and rainfall by cross-correlation analysis (Campania, southern Italy)

The relation between rainfall and the discharge from two springs, located at the base of different karst massifs in southern Italy, is investigated by cross-correlation analyses. Data are derived from a continuous time window of 13 years. The input signal involves multiple rainfall time series (cumulative rainfall over varying time windows), while the time series of daily spring discharges are used as the output signal. Analyses were first conducted on the unprocessed data and then on data for which linear trends and seasonal components had been removed, the latter by a spectral analysis. Analyses contributed to the investigation of the time required for water to flow through the karst aquifers at the two sites. Long time intervals of the cumulative rainfall (\u3e60 days) appear to be the main component affecting the spring discharge hydrographs; shorter time intervals seem to be related to quick-flow paths. Some statistics about the linear regression and the meaning of the cross-correlation analysis are discussed. Cross-correlation analysis can provide strong support for identification of the main rainfall contribution and the travel time through the main infiltration pathways in aquifers

Data-driven analysis of discharge variations at Mercure spring (South Italy)

Mercure Spring is the spillway of the carbonatic karst aquifer hosted in the north-western side on Mount Pollino (South Italy). An evolutionary data-driven paradigm is here used in order to model spring response to rainfall. The proposed analysis shows how to reliably model the short-term discharge variations of Mercure spring and that variations are related to quite short underground flow-paths, and medium length flow-paths. All the obtained results are structurally simple and the involved terms are really similar. Finally, the identified models are consistent with past studies and with the hydrogeological characteristics of the aquifer